PMID- 11032903 OWN - NLM STAT- MEDLINE DCOM- 20001109 LR - 20190630 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 75 IP - 5 DP - 2000 Nov TI - Coordinated expression of beta-amyloid precursor protein and the putative beta-secretase BACE and alpha-secretase ADAM10 in mouse and human brain. PG - 2133-43 AB - To define the enzymes involved in the etiology of Alzheimer's disease, we compared in mouse and human brain the mRNA levels and cellular localization of the ubiquitous beta-amyloid precursor protein (beta-APP) with those of the putative alpha-secretases ADAM10 and ADAM17 and the beta-secretases BACE and BACE2. In situ hybridization performed in mice during prenatal and postnatal development and in adulthood revealed the coexpression of beta-APP, BACE, and ADAM10. The patterns of BACE2 and ADAM17 only partially overlapped with that of beta-APP. beta-APP, BACE, and ADAM10 mRNAs have also been detected by northern blot in human brain cortex of normal subjects and in Alzheimer's disease subjects. In situ hybridization performed using combined biotin- and radiolabeled riboprobes provided evidence for the coexpression of beta-APP with BACE and ADAM10 in human cortical neurons. Our data provide cytochemical evidence supporting the role of ADAM10 and BACE as authentic alpha- and beta-secretases. FAU - Marcinkiewicz, M AU - Marcinkiewicz M AD - Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada. Marcinm@ircm.qc.ca FAU - Seidah, N G AU - Seidah NG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Glycoproteins) RN - 0 (Membrane Proteins) RN - 0 (RNA, Messenger) RN - EC 3.4.- (Amyloid Precursor Protein Secretases) RN - EC 3.4.- (Endopeptidases) RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) RN - EC 3.4.23.45 (BACE2 protein, human) RN - EC 3.4.23.46 (BACE1 protein, human) RN - EC 3.4.23.46 (Bace1 protein, mouse) RN - EC 3.4.24.- (ADAM Proteins) RN - EC 3.4.24.- (Metalloendopeptidases) RN - EC 3.4.24.81 (ADAM10 Protein) RN - EC 3.4.24.81 (ADAM10 protein, human) RN - EC 3.4.24.81 (Adam10 protein, mouse) RN - EC 3.4.24.86 (ADAM17 Protein) RN - EC 3.4.24.86 (ADAM17 protein, human) RN - EC 3.4.24.86 (Adam17 protein, mouse) SB - IM MH - ADAM Proteins MH - ADAM10 Protein MH - ADAM17 Protein MH - Aged MH - Alzheimer Disease/metabolism MH - Amyloid Precursor Protein Secretases MH - Amyloid beta-Protein Precursor/*biosynthesis/genetics MH - Animals MH - Aspartic Acid Endopeptidases/*biosynthesis/genetics MH - Autoradiography MH - Blotting, Northern MH - Brain/embryology/*metabolism/pathology MH - Endopeptidases/*biosynthesis/genetics MH - Frontal Lobe/metabolism MH - Gene Expression MH - Glycoproteins/biosynthesis/genetics MH - Humans MH - In Situ Hybridization MH - Membrane Proteins/*biosynthesis/genetics MH - Metalloendopeptidases/*biosynthesis/genetics/metabolism MH - Mice MH - Middle Aged MH - Neurons/cytology/metabolism MH - Parietal Lobe/metabolism MH - RNA, Messenger/metabolism EDAT- 2000/10/18 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/10/18 11:00 PHST- 2000/10/18 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/10/18 11:00 [entrez] AID - 10.1046/j.1471-4159.2000.0752133.x [doi] PST - ppublish SO - J Neurochem. 2000 Nov;75(5):2133-43. doi: 10.1046/j.1471-4159.2000.0752133.x.